ORIGINAL PAPER Natural endogenous ligands for benzodiazepine receptors in hepatic encephalopathy M. Baraldi & R. Avallone & L. Corsi & I. Venturini & C. Baraldi & M. L. Zeneroli Received: 2 April 2008 / Accepted: 28 October 2008 / Published online: 11 December 2008 # Springer Science + Business Media, LLC 2008 Abstract Benzodiazepines of natural origin (NBZDs) have been found in human blood and brains as well as in medicinal plants and foods. In plasma and brain tissue there are i.e. diazepam and nordiazepam equal to commercial drugs but there are also other benzodiazepine-like compounds termed “endozepines”, which act as agonists at the benzodiazepine receptors of central type (CBR). A synthetic pathway for the production of NBZDs has not yet been found, but it has been suggested that micro- organisms may synthesize molecules with benzodiazepine-like structures. Hence NBZDs could be of both endogenous and exogenous source and be considered as natural anxyolitic and sedative. Interestingly there are also natural compounds, such as the polypeptide Diazepam Binding Inhibitor (DBI) acting as an “inversive agonist” implicated in fair and panic disorders. It has been suggested that NBZDs may play a role in the pathogenesis of hepatic encephalopathy (HE). Multidirectional studies Metab Brain Dis (2009) 24:81–93 DOI 10.1007/s11011-008-9111-8 M. Baraldi (*) : R. Avallone : L. Corsi Department of Biomedical Sciences (Section of Pharmacology), University of Modena and Reggio Emilia, Via Campi 287, 41100 Modena, Italy e-mail: mario.baraldi@unimore.it R. Avallone e-mail: rossella.avallone@unimore.it L. Corsi e-mail: lorenzo.corsi@unimore.it I. Venturini : M. L. Zeneroli Department of Internal Medicine, University of Modena and Reggio Emilia, Via Campi 287, 41100 Modena, Italy I. Venturini e-mail: ivo.venturini@policlinico.mo.it M. L. Zeneroli e-mail: marialuisa.zeneroli@unimore.it C. Baraldi Department of Surgery (Transplantation Unit), University of Modena and Reggio Emilia, Modena, Italy e-mail: claudia.baraldi@unimore.it